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Better Cancer Monitoring with Cell-Free DNA
November 2014
Forward-Looking Statements
Statements in this presentation about the Company's expectations, applications of its
technology, markets, launch of tests and other statements that are not historical facts are
"forward-looking statements" within the meaning of Section 27A of the Securities Act of
1933 and Section 21E of the Securities Exchange Act of 1934 and are based on
management's current beliefs, assumptions, estimates and projections.
Actual results may differ materially from those projected in the forward-looking statements
for various reasons, including risks associated with product and test development, test
transfer to contracting labs, government regulation, market acceptance, limited commercial
experience, dependence on key personnel, obtaining financing and other factors discussed
in the Company's periodic reports filed with the Securities and Exchange Commission.
Copyright©2014 Trovagene, Inc. | Confidential
2
Our Goal
To Improve Treatment Outcomes with
Non-invasive Cancer Monitoring
Trovagene’s technology non-invasively detects and
quantitates circulating tumor DNA in urine and plasma for
improved disease management
Copyright©2014 Trovagene, Inc. | Confidential
3
Company Overview
Significant patent
portfolio around
cell-free DNA
Precision cancer monitoring
technology addresses a high
unmet clinical need
Enables frequent, non-invasive
monitoring of oncogene mutation
status, disease progression, and
recurrence
Numerous clinical collaborations
with leading cancer centers
Proprietary methods of
extracting, purifying,
detecting and quantifying
oncogene mutations in
cell-free DNA
NASDAQ: TROV
$135M market cap*
Molecular Diagnostic Specialist
Focused on Cancer Monitoring
30+ clinical studies
Founded in 1999
Expanding clinical evidence to
support broad market adoption
NASDAQ listing 2012
$31M cash on hand (as of
09/30/14)
Generating health economic data
necessary for appropriate
reimbursement
*fully diluted as of 10/30/14
CLIA certified, CAP
accredited, high
complexity lab to offer
diagnostic services
Copyright©2014 Trovagene, Inc. | Confidential
4
Experienced Leadership Team
Antonius Schuh PhD
Mark Erlander PhD
Stephen Zaniboni
Scientific Advisors
Chief Executive Officer
Chief Science Officer
Chief Financial Officer
Alberto Bardelli, PhD
Sorrento Therapeutics, AviaraDx,
Arcturus, Sequenom
BioTheranostics, AviaraDx, Arcturus,
J&J, Scripps Research Institute
Awarepoint, XIFIN,
Sorrento Therapeutics,
AviaraDx, Arcturus, Sequenom
Paul Billings, MD, PhD
PhD Pharm. Chem
BS, MS Biochem | PhD Neuroscience
CPA | BS Accounting | MBA
Riccardo Dalla-Favera, MD
Charles Cantor, PhD
Carlo M. Croce, MD
Brunangelo Falini, MD
Oanh Dang PhD
Vlada Melnikova MD, PhD
Keith McCormick
VP, Business Development
VP, Research & Development
VP, Sales/Mktg
Sequenom, Gen-Probe, Illumina,
Sirius Genomics, Zymeworks
Transgenomic, ApoCell,
MD Anderson Cancer Center
PhD Biomedical Sciences
MD | PhD Biological Engineering
BioTheranostics, AviaraDx, Biogen
Idec, Schering Plough, Dianon
Systems
BBA Marketing | MBA Int’l Business
K. Peter Hirth, PhD
Board of Directors
Thomas Adams, PhD (Chair)
Paul Billings, MD, PhD
John P. Brancaccio, CPA
David Moskowitz
Gary S. Jacob, PhD
VP, Investor Relations
Rodney Markin, MD, PhD
UBS, FBR, Caris&Co, Roth Capital
Antonius Schuh, PhD
BS Pharmacy | MBA Finance
Copyright©2014 Trovagene, Inc. | Confidential
Stanley Tennant, MD
5
Clinical Problem
Targeted Therapies for
Cancer
New Understanding of Cancer
Driven by
Oncogene mutations
and alterations
Heterogeneous:
Intra-tumor
Inter-tumor
(Distal)
Copyright©2014 Trovagene, Inc. | Confidential
Need for
Genomic
Monitoring
•
Therapies are expensive and
have side effects
•
Specific for particular biomarkers
•
Response monitoring required
•
Resistance develops
6
Limitations of Current Technology for Cancer Monitoring
Imaging
Tissue biopsy
Circulating
tumor cells
Traditional
blood markers
• Rough indication
of tumor size
• Invasive procedures, often
not possible
• Not representative of
tumor heterogeneity
• Not representative of
tumor heterogeneity
• No molecular information
• Potential for serious
complications
• Not informative of tumor
dynamics
• Non-specific for cancer
• Serial biopsies increasingly
not feasible
• Low clinical sensitivity
• Radiation concerns for
younger patients
• Low clinical sensitivity
• Technically challenging
• Not representative of tumor
heterogeneity
Copyright©2014 Trovagene, Inc. | Confidential
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Significant Market Opportunity
Insufficient Imaging Tools in Oncology
Still Yield Huge Market
$12B
Initial Opportunity for Trovagene
525K
Metastatic cancer
patients per year
In 2010
8-10
• Cancer already in advanced state
• No molecular data delivered
$5B
Imaging procedures
received by cancer
patient during first year
of treatment
Potential market
Source: BCC Research
Copyright©2014 Trovagene, Inc. | Confidential
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ctDNA Emerging as Preferred Analyte to Monitor Cancer
“Cancer is a disease of DNA…
defining cancer by what tissue
it arose in is going to go by the
boards pretty soon.”
“Circulating tumor DNA levels
showed a greater dynamic
range, and greater correlation
with changes in tumor burden,
than did CA 15-3 or circulating
tumor cells.”
“The statistically significant
correlation between mutational
status and treatment response
suggests oncogene mutation
monitoring using urinary cell-free
DNA can help clinicians rapidly
determine responders from
non-responders, [to] improve
patient outcomes”.
Dr. Frances Collins, National Institutes of
Health (NIH) Director, ‘Politics on The
Frontier of Science’, Wall Street Journal,
November 8, 2013
Sarah-Jane Dawson et. al., Analysis of
Circulating Tumor DNA to Monitor Metastatic
Breast Cancer, NEJM, Vol. 368, No. 12,
March 2013
Filip Janku M.D., Ph.D et al., 2014 ASCO
Annual Meeting Proceedings,
a Journal of Clinical Oncology
Sci Transl Med. 2014 Feb 19;6(224):224ra24. N Engl J Med 2013; 368:1199-1209 Sci. Transl. Med. 4, 136ra68 (2012).
Copyright©2014 Trovagene, Inc. | Confidential
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Circulating Tumor DNA (ctDNA)
Tumor cells
Main Advantages
of ctDNA
• Captures intratumor
heterogeneity
• Systemic overview of
cancer
• Frequent sampling
options for monitoring
applications
• Different analyte options
depending on clinical
context
Copyright©2014 Trovagene, Inc. | Confidential
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Why Urine?
15,000 –
150,000 genome
equivalent
3,000 –
15,000 genome
equivalent
Plasma
Urine
ctDNA
ctDNA
Unlimited Volume
Frequency of Testing
Completely Non-invasive
Convenient
Copyright©2014 Trovagene, Inc. | Confidential
11
SM
Trovagene Precision Cancer Monitoring (PCM ) Platform
Extraction and Isolation
of ctDNA
Mutant Allele Enrichment
Platform Agnostic
Detection and
Quantification
59%
ctDNA 2.0 ng/ul
gDNA 1.4 ng/ul
92%
ctDNA 4.9 ng/ul
Proprietary error rate
detection and
normalization.
gDNA 0.04 ng/ul
~0.5µg ctDNA/
100 mL of urine
100-1000 fold
enrichment
Integration with Commercially
Available Platforms
Single Molecule Detection
Ultra-Sensitive Detection and Quantitative Monitoring
Copyright©2014 Trovagene, Inc. | Confidential
12
Patent Portfolio
Patent Families
Patent Term
Term to approx. 2035
Concentrating Urine Family
US provisional app filed
Term to approx. 2034
51-110 bp TrNA Family
US provisional app filed
Term to approx. 2034
Small Footprint Family
US provisional app filed
Term to approx. 2034
Monitoring Disease Family
US provisional app filed
Term to approx. 2029
20-50 bp TrNA Family
US & EU
Term to approx. 2027
Anion Exchange Purification Family
Viral and Pathogen TrNA Families
TrNA Patent Family
US, EU, Canada
Term to approx. 2026
US, EU, JP, China, Australia, Canada,
India
Term 2018
US & EU
Copyright©2014 Trovagene, Inc. | Confidential
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Strategy to Drive Clinical Adoption & Reimbursement
QUALITATIVE
QUANTITATIVE
STANDARD OF CARE
Stage 1
Stage 2
Stage 3
Tumor Status
Tumor Dynamics
Improved Patient Outcomes
• Demonstrate concordance of oncogene
mutation status between
urine and tumor tissue
• Expand mutational coverage of
urine-based actionable oncogene mutations
for our PCM platform
• Clinical Utility:
Determine mutational status of actionable
biomarkers in urine when a biopsy is not
an option. Ex. BRAF, KRAS
• Clinical Utility:
Quantitatively assess mutational status
in urine longitudinally as an indicator
of responsiveness to therapy,
disease status & emergence
of resistance mutations
$100$200M
Revenue
Copyright©2014 Trovagene, Inc. | Confidential
$500+M
Revenue
• Demonstrate in multi-institutional trials that
results from urine-based monitoring of
actionable mutations increases patient
progression-free survival (PFS) & overall
survival (OS)
• Demonstrate health economic benefits of
non-invasive oncogene mutation monitoring
• Clinical Utility:
Quantitatively assess patient mutational status
in urine longitudinally for mutational status and
early detection of resistance to therapy as
a decision tool for therapy selection
Multi
$B
Revenue
14
SM
30+ Collaborations to Validate & Integrate our PCM Platform
Ongoing
Pending
Protocol in
Dev/Approval
Under
Evaluation
Lung Cancer
(NSCLC)
4
3
─
399,000
Colorectal
Cancer
4
3
─
1,154,000
Pancreatic
Cancer
3
─
1
42,000
Melanoma
2
4
─
922.000
ECD/LCH
2
─
1
5,000
Brain Cancer
1
1
─
142,000
Prostate
Cancer
─
1
─
2,618,000
All-Comers,
Metastatic
Cancers
2
─
─
525,000
HPV
2
─
3
Total # of
Studies
20
12
5
Disease
Copyright©2014 Trovagene, Inc. | Confidential
Market
Size U.S.
(# of pts)
15
Increasing Volume of Clinical Study Samples Received
3,000
2,759
# CUMULATIVE SAMPLES
2,500
2,000
1,582
1,500
927
1,000
473
500
13
127
0
Jul '13
Copyright©2014 Trovagene, Inc. | Confidential
Oct '13
Jan '14
Apr '14
Jul '14
Oct '14
16
Clinical Results Presented & Published To Date
8/2014
4/2014 AACR Poster
NEXTGEN DX SUMMIT
Oral Presentation, Technology
Concordant BRAF
Initial concordance with
plasma and tissue
2 ASCO Presentations
6/2014
1. Histiocytic BRAF
MSKCC/MD Anderson
Publication
2. Longitudinal BRAF
MD Anderson
10/2014 Cancer Discovery
Histiocytic BRAF
Publication
5/2014
Oncotarget
IPV Meeting
Histiocytic BRAF
MD Anderson
Initial longitudinal data—
concordance with imaging
8/2014 Poster Presentation
HR-HPV
Publication
5/2014
ECD guideline
Blood
ECD clinical guidelines
2014
Q1
Q2
Copyright©2014 Trovagene, Inc. | Confidential
Q3
Q4
17
High Concordance of KRAS Status in Urine, Plasma & Tissue
of Advanced Colorectal Cancer Patients
20 Advanced Stage Colorectal Cancer Patients
KRAS Mutation in Tissue, Treatment Naïve
Matched urine and plasma, archived (3-5 years)
Blinded analysis, seven KRAS mutations (G12A/C/D/R/S/V and G13D)
20 Urine
Evaluable urine
n = 16

Urine vs. Tissue biopsy
Concordant
KRAS mutation
15/16
94%
Copyright©2014 Trovagene, Inc. | Confidential
20 Plasma
Non-evaluable urine
n=4
X
Urine vs. Plasma
Concordant
KRAS mutation
15/16
94%
Plasma vs. Tissue biopsy
Concordant
KRAS mutation
19/20
95%
18
Monitoring ctBRAF V600E and Treatment Response
17 metastatic cancer patients
Positive urine BRAF V600E
15 evaluable patients for ctDNA BRAF V600E ≥4 weeks
Evaluate time to progression
Urine ctDNA
BRAF decrease
Urine ctDNA
BRAF increase
259 days (median)
to progression
95% CI=240-278 days
61 days (median)
to progression
95% CI = 59-63 days
% tumor change per RECIST 1.1
Urine BRAF V600E ctDNA
monitoring has clinical utility to
track therapeutic efficacy of
metastatic cancer patients
harboring mutant BRAF V600E
Urine BRAF ctDNA
correlates to
BRAF/MEK targeted
therapy (p=0.002)
p=0.002
Copyright©2014 Trovagene, Inc. | Confidential
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ctDNA Improves Genotyping Over Tissue Biopsies in Histocytic Patients
BRAFV600E burden in urine correlates
w/ radiographic response.
Tissue BRAFV600E genotype
Indeterminate
Genotype
n=9
n=15
BRAF
Wildtype
BRAFV600E
Mutant
n=6
Urinary ctDNA BRAFV600E genotype
n=16
BRAF
Wildtype
n=14
BRAFV600E
Mutant
1 Abdel-Wahab
Copyright©2014 Trovagene, Inc. | Confidential
et al., ASCO Poster Highlight 2014
20
Dynamic Monitoring Captures Early Progression and Response
Successful monitoring tumor dynamics
independent of drug class used
Patient’s tumor progressed within
1 wk of Anakinra withdrawal
• Demonstration of need for higher
frequency urine-based testing to monitor
Patient responded to Vemurafenib,
BRAF inhibitor
One week
• Demonstrates that continually
monitoring patient enables optimal
therapy over time
1 Abdel-Wahab
Copyright©2014 Trovagene, Inc. | Confidential
et al., ASCO Poster Highlight 2014
21
Current Development Program for Cancer Monitoring Applications
KRAS Exon 2
Copyright©2014 Trovagene, Inc. | Confidential
BRAF V600E
KRAS Exon 2,3,4
EGFR Exon 20 T790M
NRAS Exon 2
NRAS Exon 2,3,4
EGFR Exon 19 Del
BRAF V600E
EGFR Exon 21 L858R
PIK3CA H1047R
ALK Rearrangements
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Ongoing Clinical Utility Studies
Cancer Type/Institution
Detection of Mutation
Monitoring Tumor Load
Emergence of
Resistant Mutations
Biomarker
Clinical Utility Examined
# Patients Expected
Pancreatic/MDACC
KRAS
Minimal residual disease detection post surgery
90
Brain/UCSD
BRAF
Detect ctDNA in brain cancer patients
5
Lung/MSKCC
EGFR
Detection and monitoring of EGFR mutations
200
All Comers/MDACC
BRAF/KRAS
Faster assessment of therapeutic efficacy
185
Pancreatic/USOR-SH-UCSF
KRAS
Monitor disease burden by ctDNA vs. CA19-9
45
Melanoma/DFCI
BRAF
ctDNA avoids immunotherapy “pseudo-progression”
40
Lung/Pharma
EGFR T790M
Predict initial/clinical response of new therapeutic
375
Colorectal/GRI
KRAS
Correlate ctDNA to Tx response/PD/recurrence
54
Pancreatic/U. Copenhagen
KRAS
Correlate ctDNA to Tx response/PD/recurrence
1000
Lung/Catholic Health Initiatives
EGFR
Non-responders to EGFR activating mutations to Tx
30
Colorectal/ USC
KRAS
Emergence of mutant KRAS on anti-EGFR Tx
60
CRC and others/ONG-INB
KRAS/BRAF
Monitor tumor dynamics and acquired resistance
40
Lung/MSKCC
EGFR T790M
T790M detection prior to radiological progression
25
Copyright©2014 Trovagene, Inc. | Confidential
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Ongoing Clinical Studies Continue to Drive Publications
ASCO GI
EORTC-NCI-AACR
11/2014 Abstract(s)
10/2014
1/2015 Abstract accepted
HISTIOCYTIC SOC.
Abstract
ECD/LCH BRAF
MSKCC/MDACC
Submit manuscript
HR-HPV Method
Submit manuscript
Longitudinal KRAS
Pancreatic
Submit manuscript
Detection T790M
Lung
Submit manuscript
Longitudinal KRAS
Colorectal
Submit manuscript
HR-HPV Predictor4
Q4
2014
5/2015
EUROGIN
2/2015 Abstract Submitted
Submit manuscript
Longitudinal KRAS
Pancreatic
Submit manuscript
Longitudinal KRAS
Colorectal
NEXTGEN DX SUMMIT
8/2015 Submit abstract
AACR Poster
4/2015 Submit abstracts
Q1
4/2015
ASCO
Submit abstracts
Melanoma, lung, pancreatic
colorectal cancers
European Lung
Cancer Conference
Submit abstracts
9/2015
EORTC-NCI-AACR
Submit abstracts
ESMO
Submit abstracts
10/2015
9/2015
Submit manuscript
Submit manuscript
Longitudinal and pharmacodynamic
EGFR monitoring lung cancer
BRAF and KRAS multiple cancers
MD Anderson
Submit manuscript
KRAS/BRAF colorectal
Technology comparison study
Q2
3/2015
Technology
Q3
IPV Conference
Submit Abstracts
HISTIOCYTIC SOC.
Submit abstracts
th
9/2015 16 World Conference on Lung Cancer
Submit abstracts
10/2015
Chicago Multidisciplinary
Symposium in Thoracic
Oncology
Submit abstracts
Q4
2015
Copyright©2014 Trovagene, Inc. | Confidential
24
Market Development Activities for Commercialization Program
Market Development (2013-2014)
Full Commercialization (2015)
• Relationships w/ 30+ top cancer centers
– 17 National Comprehensive Cancer Network
(NCCN) Centers
Target KOLs/
Early adopters
Develop IIS
(Investigator Initiated Study)
Program
• 100+ oncologists engaged in outreach
• Signed partnership w/ 2 major IDNs
– CHI (Catholic Health Initiative)
• 93 hospitals
– Lurie Cancer Center of Northwestern Univ.
Accelerate Adoption
within Integrated
Healthcare Delivery
Networks (IDNs)
Copyright©2014 Trovagene, Inc. | Confidential
Branding,
Market Awareness
and Education
25
Key Components for Full Commercialization in 2015
Full Commercialization (2015)
• Direct sales team
– 6 sales reps in Phase 1
– Headcount ramp to be initiated in Q1 2015
Drive Adoption of
Expanded Menu
Expand New
Market Segments
Copyright©2014 Trovagene, Inc. | Confidential
Conversion of Research
Collaborators to
Clinical Adopters
• Direct coverage of top target sites
–
–
–
–
Major academic cancer centers
Entire ECD/LCH treating physician base
IDNs where TROV has relationships
Geographic focus on key oncology markets
New Market for
Genomic Monitoring
26
Reimbursement Value Based on Clinical Utilities of ctDNA
Detection of Mutation
When tissue biopsy
is unavailable
Supplement tissue biopsy
to get systemic overview
of the entire heterogeneity
of cancer
Monitoring Tumor Size
Tumor load
Emergence
of resistant
mutations
Drug holidays
Repeat Testing: Novel Utility
Once Clinical Data
Established,
Reimbursement:
Tier 1 MDx Codes
Concordance with SOC
Established codes
Price/assay
Copyright©2014 Trovagene, Inc. | Confidential
1. Not Otherwise Classified Codes (NOC)
2. Unique CPT Codes
27
Trovagene Urine-based High Risk HPV Assay
Cervical Cancer
HPV Testing Market Globally
265K
$6B
$9B
Deaths in
2012
Market in
2013
Market in
2020
Urine-based High Risk HPV Assay established
in Trovagene’s CLIA lab since 2013
New Clinical Evidence
• Screening is a viable solution:
75% reduction in incidence in US from 1940 to
1980 w/ National Screening Program
NCI:
Comparative Urine
Study
J Clin Virol. 2014 Aug;60(4):414-7
UNC:
Urine collection
methodology for detecting
HPV associated with
CIN2+/CIN3
• Screening not available globally:
–
Cost, Technical expertise, Healthcare infrastructure, Quality
Control, Cultural
• High-risk HPVs cause virtually all cervical cancers
Queen Mary, UL:
High sensitivity of test for detecting HPV associated
with CIN2+, CIN3 (malignancy)
Source: Transparency Market Research
Copyright©2014 Trovagene, Inc. | Confidential
28
Developing Trovagene’s HPV Franchise
Internal Development
1. Clinical studies in general screening population
•
Strand Life Sciences
(3,000 patients, enrollment underway)
•
Planning stages for pivotal studies
Partnering Opportunities
Strategic partners to
commercialize the test globally
2. Obtain regulatory compliance
CE Mark
Copyright©2014 Trovagene, Inc. | Confidential
FDA
29
Catalysts & Milestones to Drive Valuation
Demonstrate
clinical utility
• 20+ abstracts and
manuscripts in 2015
Expand mutation
coverage on
PCM platform
Initiate new
collaborations to
establish
clinical utility
Establish strategic
partnerships to grow
market reach
Drive early adoption
in top cancer centers
and integrated
healthcare networks
• 8 New Menu Assays
• 10+ clinical studies in
2015
• Geographic
expansion
• Top academic
centers
• Kit manufacturing
• Commercial presence
in 20 cancer centers
with repeat revenue
• Pharma collaboration
• HPV collaboration
Copyright©2014 Trovagene, Inc. | Confidential
30
For further information
Please contact:
Stephen Zaniboni, CFO
[email protected]
Antonius Schuh, CEO
[email protected]
David Moskowitz, VP, Investor Relations
[email protected]